Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, India; Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rishikesh, India.
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Rishikesh, India.
J Steroid Biochem Mol Biol. 2020 May;199:105588. doi: 10.1016/j.jsbmb.2020.105588. Epub 2020 Jan 28.
Multiple myeloma (MM) is a plasma cell malignancy frequently accompanied with skeletal co-morbidity. Vitamin D (1,25(OH)D) is an important mediator of skeletal homeostasis that mediates its effect by binding to vitamin D receptor (VDR), a steroid family receptor and modulates various downstream pathways. Multiple polymorphisms have been determined in VDR gene that witnessed significant association with cancer development and progression. Therefore, in this maiden study, we recruited 75 newly diagnosed MM patients and 75 control subjects. 25-hydroxy vitamin D (25(OH)D) levels were measured in all recruited study subjects. Further, PCR-RFLP was performed in DNA samples of recruited study subjects. Results demonstrated significantly decreased 25(OH)D levels in MM patients compared to controls. Additionally, decreased 25(OH)D levels in MM patients inversely associated with disease severity. Further, single nucleotide polymorphism (SNP) analysis of VDR gene showed significantly higher risk of MM disease development in Ff + ff, Aa + aa, and Bb + bb genotypes. Additionally, FokI f, ApaI a and BsmI b alleles were significantly associated with MM occurrence. In conclusion, this study provided initial evidences of association between 25(OH)D insufficiency, VDR gene polymorphism and MM development. Thus, we suggest that a study involving assessment of 25(OH)D levels and VDR gene polymorphism in large patients' cohort might substantiate their role in MM development which would further provide impetus to give 25(OH)D supplementation along with conventional chemotherapeutic agents for myeloma treatment in future.
多发性骨髓瘤（MM）是一种常伴有骨骼合并症的浆细胞恶性肿瘤。维生素 D（1,25（OH）D）是骨骼稳态的重要调节剂，通过与维生素 D 受体（VDR）结合发挥其作用，VDR 是一种甾体家族受体，调节各种下游途径。VDR 基因中已确定了多种多态性，这些多态性与癌症的发生和发展有显著关联。因此，在这项初步研究中，我们招募了 75 名新诊断的 MM 患者和 75 名对照。所有入组研究对象均测量了 25-羟维生素 D（25（OH）D）水平。此外，还对入组研究对象的 DNA 样本进行了 PCR-RFLP 分析。结果表明，与对照组相比，MM 患者的 25（OH）D 水平显著降低。此外，MM 患者的 25（OH）D 水平降低与疾病严重程度呈负相关。此外，VDR 基因的单核苷酸多态性（SNP）分析表明，FF+FF、AA+AA 和 BB+BB 基因型的 MM 发病风险显著增加。此外，FokI f、ApaI a 和 BsmI b 等位基因与 MM 的发生显著相关。总之，这项研究提供了 25（OH）D 不足、VDR 基因多态性与 MM 发病之间关联的初步证据。因此，我们建议在更大的患者队列中进行 25（OH）D 水平和 VDR 基因多态性评估的研究，可能证实它们在 MM 发病中的作用，这将进一步推动在未来的骨髓瘤治疗中，将 25（OH）D 补充与常规化疗药物联合使用。
